An active peptide purified from gastrointestinal enzyme hydrolysate of Pacific cod skin gelatin attenuates angiotensin-1 converting enzyme (ACE) activity and cellular oxidative stress

► Gelatin was isolated from sea food processing by-product, Pacific cod skin. ► Extracted gelatin was hydrolysed with gastro-intestinal endo-peptidases. ► Active peptide Leu-Leu-Met-Leu-Asp-Asn-Asp-Leu-Pro-Pro was isolated. ► Peptide showed potent non-competitive ACE inhibitory activity (IC50-35.72μM). ► Peptide protected the cellular macromolecules from oxidative damage. Seafood processing by-product, Pacific cod (Gadus macrocephalus) skin, was utilised to purify an active peptide with ACE inhibitory and antioxidant activities. Gelatin was extracted from the skin and it was hydrolysed with gastrointestinal endopeptidases (pepsin, trypsin and α-chymotrypsin). Assay-guided purification of the hydrolysate resulted in an active peptide, Leu-Leu-Met-Leu-Asp-Asn-Asp-Leu-Pro-Pro (1301Da). The peptide showed potent non-competitive ACE inhibition (IC50=35.7μM) and effectively protects cellular macromolecules from reactive oxygen species (ROS) mediated damage. The peptide significantly reduced the oxidation levels of membrane lipids, proteins and DNA in RAW264.7 cells by effectively scavenging the intracellular ROS. Moreover, it was found that the peptide treatment upregulated the m-RNA expression of cellular antioxidative enzymes (superoxide dismutase, glutathione and catalase) and thereby enhanced the intracellular antioxidant mechanisms. These findings suggest that Pacific cod skin could be effectively bioconverted to produce a bioactive peptide, which could be used as a functional food ingredient to control ACE activity and oxidative stress.